$Unique_ID{BRK03931} $Pretitle{} $Title{Lesch-Nyhan Syndrome} $Subject{Lesch-Nyhan Syndrome Hereditary Hyperuricemia Hyperuricemia Choreoathetosis Self-mutilation syndrome Hyperuricemia-Oligophrenia Nyhan syndrome Juvenile Gout Choreoathetosis Mental Retardation syndrome } $Volume{} $Log{} Copyright (C) 1986, 1990 National Organization for Rare Disorders, Inc. 255: Lesch-Nyhan Syndrome ** IMPORTANT ** It is possible the main title of the article (Lesch-Nyhan syndrome) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Hereditary Hyperuricemia Hyperuricemia, Choreoathetosis, Self-mutilation syndrome Hyperuricemia-Oligophrenia Nyhan syndrome Juvenile Gout, Choreoathetosis, Mental Retardation syndrome General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Lesch-Nyhan syndrome is a sex-linked hereditary neurological disorder caused by an enzymatic defect. Onset occurs during infancy and it progresses to cause aggressive behavior (including self-mutilation) and mental retardation. Symptoms Onset of Lesch-Nyhan syndrome occurs during infancy in males. Babies affected by the disorder usually appear normal and healthy until they are a few months old when their condition begins to deteriorate. The defect in the enzyme that causes Lesch-Nyhan syndrome can be detected with almost 100% accuracy in people affected by the syndrome and in carriers through a biochemical study on cultured cells. This defect causes a marked elevation of uric acid in their blood (hyperuricemia). Affected male babies can be detected before birth through the same test. Orange sand (from the urine) in the diaper is usually the first sign of the disorder. Stones in the urine (urolithiasis) and the appearance of chalky deposits of sodium urate (tophi) around joints and under the skin occur as early as age 8 years. As a consequence, kidney disease and arthritis (gout) may develop. Patients exhibit a startle reaction with arching of the head and back in response to sudden noise. They suffer from muscular weakness and perform ceaseless slow writhing movements of the fingers, arms, toes and face. Speech and swallowing becomes impaired. Patients vomit frequently. Most children with the Lesch-Nyhan syndrome are severely underweight, and many are quite short. In addition, part of the respiratory tract is constricted and the breath makes a whistling sound (aspiration). Pneumonia is common in patients with this disorder. A peculiar characteristic of this syndrome is outbursts of aggressive behavior including self-mutilation. The children must be protected from themselves. Causes Lesch-Nyhan syndrome is an X-linked hereditary disorder caused by a lack of hypoxanthine-guanine posphoribosyl transferase enzyme which participates in the metabolism of acid purines. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males have only one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons.) People affected with the disorder, or carriers, can be detected through biochemical studies on cultured cells, even before birth. Female siblings and maternal aunts can be carriers of the disorder, but usually only males get Lesch-Nyhan syndrome. Affected Population Lesch-Nyhan syndrome affects only males, though females can be genetic carriers of the disorder. Therapies: Standard Allopurinol is used to treat the symptoms related to excessive production of uric acid in Lesch-Nyhan syndrome. Children with this disorder require physical restraints such as hip, chest and elbow restraints so they do not hurt themselves. Elbow restraints keep the hands free. Biting of fingers and/or lips can be prevented by extracting teeth. Therapies: Investigational Investigational studies with a mouse virus are underway. If this virus is injected into humans, it is hoped that it may trigger production of the enzyme lacking in patients with Lesch-Nyhan syndrome. This study is in its initial stages, and it may be some years before the technique moves out of the laboratory and into clinical trials. This disease entry is based upon medical information available through April 1990. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Lesch-Nyhan Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Lesch-Nyhan Syndrome Registry Dr. Lowell Anderson New York University School of Medicine Bellevue Hospital Medical Center Dept. of Psychiatry 550 First Ave. New York, NY 10012 (212) 263-6458 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 Dr. William L. Nyhan Professor of Pediatrics UC School of Medicine, San Diego CA La Jolla, CA 92093 (619) 534-4150 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References Disorders of Purine and Pyrimidine Metabolism: Nyhan, in: Practice of Pediatrics: Kelley, Harper & Row (1982).